Boc-D-Met(O2)-OH

Background: This review article deals with the role of calcium in ischemic cell death. A calcium-related mechanism was proposed more than two decades ago to explain cell necrosis incurred in cardiac ischemia and muscular dystrophy. In fact, an excitotoxic hypothesis was advanced to explain the acetylcholine-related death of muscle end plates. A similar hypothesis was proposed to explain selective neuronal damage in the brain in ischemia, hypoglycemic coma, and status epilepticus. Summary of review: The original concepts encompass the hypothesis that cell damage in ischemia-reperfusion is due to enhanced activity of phospholipases and proteases, leading to release of free fatty acids and their breakdown products and to degradation of cytoskeletal proteins. It is equally clear that a coupling exists between influx of calcium into cells and their production of reactive oxygen species, such as .O2, H2O2, and .OH. Recent results have underscored the role of calcium in ischemic cell death. A coupling has been demonstrated among glutamate release, calcium influx, and enhanced production of reactive metabolites such as .O2-, .OH, and nitric oxide. It has become equally clear that the combination of .O2- and nitric oxide can yield peroxynitrate, a metabolite with potentially devastating effects. The mitochondria have again come into the focus of interest. This is because certain conditions, notably mitochondrial calcium accumulation and oxidative stress, can trigger the assembly (opening) of a high-conductance pore in the inner mitochondrial membrane. The mitochondrial permeability transition (MPT) pore leads to a collapse of the electrochemical potential for H+, thereby arresting ATP production and triggering production of reactive oxygen species. The occurrence of an MPT in vivo is suggested by the dramatic anti-ischemic effect of cyclosporin A, a virtually specific blocker of the MPT in vitro in transient forebrain ischemia. However, cyclosporin A has limited effect on the cell damage incurred as a result of 2 hours of focal cerebral ischemia, suggesting that factors other than MPT play a role. It is discussed whether this could reflect the operation of phospholipase A2 activity and degradation of the lipid skeleton of the inner mitochondrial membrane. Conclusions: Calcium is one of the triggers involved in ischemic cell death, whatever the mechanism.

Abiotic stresses impact growth, development, and productivity, and significantly limit the global agricultural productivity mainly by impairing cellular physiology/biochemistry via elevating reactive oxygen species (ROS) generation. If not metabolized, ROS (such as O2 (·-), OH(·), H2O2, or (1)O2) exceeds the status of antioxidants and cause damage to DNA, proteins, lipids, and other macromolecules, and finally cellular metabolism arrest. Plants are endowed with a family of enzymes called superoxide dismutases (SODs) that protects cells against potential consequences caused by cytotoxic O2 (·-) by catalyzing its conversion to O2 and H2O2. Hence, SODs constitute the first line of defense against abiotic stress-accrued enhanced ROS and its reaction products. In the light of recent reports, the present effort: (a) overviews abiotic stresses, ROS, and their metabolism; (b) introduces and discusses SODs and their types, significance, and appraises abiotic stress-mediated modulation in plants; (c) analyzes major reports available on genetic engineering of SODs in plants; and finally, (d) highlights major aspects so far least studied in the current context. Literature appraised herein reflects clear information paucity in context with the molecular/genetic insights into the major functions (and underlying mechanisms) performed by SODs, and also with the regulation of SODs by post-translational modifications. If the previous aspects are considered in the future works, the outcome can be significant in sustainably improving plant abiotic stress tolerance and efficiently managing agricultural challenges under changing climatic conditions.

Platelet activation is a key step in the onset of cardiovascular complications in patients affected by systemic atherosclerosis. Among other mechanisms, oxidative stress seems to play a crucial role in platelet activation. Reactive Oxidant Species (ROS) including O2(-), OH(-) or H2O2 act as second messenger to activate platelets via (1) calcium mobilization, (2) nitric oxide inactivation and (3) through the interaction with arachidonic acid to give formation of isoprostanes. One important source of ROS is represented by platelet NADPH oxidase. Growing data from experimental and clinical studies provide evidence that Nox2, the catalytic core of the NADPH oxidase system, is implicated in platelet activation. Accordingly, an impaired platelet activation has been described in patients with genetically determined Nox2 deficiency. Moreover, platelets added with specific inhibitors of Nox2 revealed impaired platelet activation, along with ROS down-production. Similar results were seen in animals treated with apocynin, a Nox inhibitor, showed reduced platelet adhesion and atherosclerotic plaque. A significant association between Nox2 and platelet activation has been detected in patients with atherosclerotic diseases. The observed up-regulation of Nox2 with subsequent isoprostanes over-production in patients with cardiovascular diseases suggests the need to explore the potential benefit of targeting Nox2 as part of a holist anti-atherothrombotic strategy in patients with systemic atherosclerosis.